Significance of synergistic interaction of ionizing radiation and other unhealthy factors for strengthening of Chernobyl accident consequences

«Radiation and Risk», 2006, vol. 15, no. 1-2, pp.85-113

Authors

Petin V.G., Komarova L.N.
Medical Radiological Research Center of RAMS, Obninsk.

Abstract

The main aim of this paper is to demonstrate a possible significance of synergistic interaction of ionizing radiation and other unhealthy factors for strengthening of Chernobyl accident consequences. Basing on a numerous experimental data, the universal lows of synergism are derived, which are independent on agents applied, biological objects and effects observed. A new conception of mechanism of synergistic interaction is proposed. A mathematical model based on this conception is developed. The comparison of this model with experimental data demonstrated the applicability of the model proposed for prediction of the synergy, its highest value and the condition under which it can be achieved. A lot of universal predictions of this model have been revealed, the cardinal of which being formulated as follows. First of all, there is an optimal ratio of acting agents providing the highest synergistic effect. Secondly, any deviation of this ratio from optimal one resulted in a decrease of the synergy. And at last, the synergy de-pends on the intensity of the agents employed: at a smaller intensity of ionizing radiation or other physical factors (or the concentration of the chemical agents), one has to reduce the intensity of another factor (for instance, the acting temperature) to preserve the highest synergistic effect. These data, in principle, indicate a potential significance of synergistic interaction at low intensity of adverse factors encountered in the natural environment. Some examples of the significance of synergistic interaction of various agents for strengthening of Chernobyl accident consequences are presented.

Key words
Synergistic interaction, ionizing radiation, mechanism, intensity of agents used, Chernobyl accident, patterns of synergism.

References

1. Dineva S.B., Abramov V.I., Shevchenko V.A. Genetic consequences of the action of lead nitrate on the seeds of chronically irradiated populations of Arabidopsis thaliana. Genetics. 1993. Vol. 29. PP. 1914-1920.

2. Zhurakovskaya G.P., Petin V.G. Effect of dose rate on synergism of combined action of ionizing radiation and hyperthermia. Radiobiology. 1987. Vol. 27. PP. 487-492.

3. Zhurakovskaya G.P., Petin V.G. Dependence of the degree of synergy of the simultaneous action of UV light and hyperthermia on yeast cells on the intensity of UV light. Cytology. 1988. Vol. 30. PP. 1276-1280.

4. Kalugina A.V., Komarova L.N., Petin V.G. A mathematical description of the synergistic interaction between the temperature of the environment and microwaves during the heating of animals. Radiation Biology. Radioecology. 2002. Vol. 42. PP. 223-227.

5. Kapultsevich Yu.G. Quantitative patterns of radiation damage to cells. Moscow, Atomizdat Publ., 1978. 232 p.

6. Kolganova O.N., Zhavoronkov L.P., Petin V.G., Drozd A.I., Glushakova V.S., Parfenova T.A. Thermocompensatory reactions of rabbits to microwave irradiation at various ambient temperatures. Radiation Biology. Radioecology. 2001. Vol. 41. PP. 712-717.

7. Komarova L.N., Zhurakovskaya G.P., Petin V.G. Dependence of the synergism of the simultaneous action of ultrasound and hyperthermia on the intensity of ultrasound. Biophysics. 2000. Vol. 45. PP. 125-129.

8. Komarova L.N., Petin V.G., Thabisimova MD Recovery of yeast cells after exposure to ionizing radiation and hyperthermia. Radiation Biology. Radioecology. 2002. Vol. 42. PP. 54-59.

9. Komarova L.N., Petin V.G., Thabisimova M.D. Recovery of Chinese hamster cells under the influence of combined exposure to X-rays and chemicals. Medical Radiology and Radiation Safety. 2002. Vol. 47. PP. 17-22.

10. Korogodin V.I. Problems of postradiation recovery. Moscow, Atomizdat Publ., 1966. 391 p.

11. Krasavin EA The problem of RBE and DNA repair. Moscow, Energoatomizdat Publ., 1981. 192 p.

12. Kuzin A.M. The problem of synergism in radiobiology. Proceedings of the USSR Academy of Sciences, biological series. 1983. Vol. 4. PP. 485-502.

13. Petin V.G. Genetic control of modifications of the radiosensitivity of cells. Moscow: Energoatomizdat, 1987. 208 pp.

14. Petin V.G., Dergacheva I.P., Zhurakovskaya G.P. Combined action of ionizing radiation and other harmful environmental factors. Radiation and Risk. 2001. Issue. 12. PP. 117-134.

15. Petin V.G., Dergacheva I.P., Romanenko A.G., Ryabova S.V. A new concept for optimizing and predicting the effects of synergism under the combined effects of chemical and physical environmental factors. Russian Chemical Journal. 1997. Vol. 41. PP. 96-104.

16. Petin V.G., Zhurakovskaya G.P., Komarova L.N., Ryabova S.V. Dependence of synergy of environmental factors on their intensity. Ecology. 1998. No. 5. PP. 383-389.

17. Petin V.G., Zhurakovskaya G.P., Lisovsky M.A. Some radiobiological aspects of combined effects. Medical radiology. 1993. Vol. 38. PP. 18-22.

18. Petin V.G., Komarov V.P. Quantitative description of the modification of the radiosensitivity. Moscow, Energoatomizdat Publ., 1989. 192 p.

19. Petin V.G., Komarov V.P., Zhurakovskaya G.P. Theoretical description and experimental verification of the dependence of synergy on dose rate. In the book: "Heuristics of radiobiology." Kiev, 1988. PP. 68-81.

20. Petin V.G., Ryabchenko N.I., Surinov B.P. Concepts of synergism in radiobiology. Radiation Biology. Radioecology. 1997. Vol. 37. PP. 482-487.

21. Rassokhina A.V., Petin V.G., Zhurakovskaya G.P. The simultaneous effect of UV light and hyperthermia on yeast survival and recombination: the effect of the intensity of the agents used on their synergistic interaction. Radiation Biology. Radioecology. 2000. Vol. 40. PP. 99-104.

22. Ryabova S.V., Petin V.G. Mathematical description of the yield of mutations in the combined action of various mutagens. Genetics. 1998. Vol. 34. PP. 1151-1156.

23. Ryabova S.V., Petin V.G. The ability to predict the synergistic effects of combined effects on the organism level. Radiation Biology. Radioecology. 2000. Vol. 40. PP. 192-196.

24. Timofeev-Resovsky N.V., Ivanov V.I., Korogodin V.I. The application of the principle of getting into radiobiology. Moscow: Atomizdat, 1968. 228 p.

25. Tiunov L.A., Zherbin E.A., Zherdin B.N. Radiation and poisons. Moscow: Atomizdat, 1977. 144 p.

26. Thabisimova M.D., Komarova L.N., Petin V.G. Dark restoration of diploid yeast cells after simultaneous exposure to ultraviolet radiation and hyperthermia. Cytology. 2002. Vol. 44. PP. 555-560.

27. Ben-Hur E. Mechanisms of the synergistic interaction between hyperthermia and radiation in cultured mammalian cells. J. Radiat. Res. 1976. Vol. 17. PP. 92-98.

28. Ben-Hur E., Elkind M.M., Bronk B.V. Thermally enhanced radioresponse of cultured Chinese hamster cells: inhibition of repair of sublethal damage and enhancement of lethal damage. Radiat. Res. 1974. Vol. 58. PP. 38-51.

29. Chameaud J., Perraud R., Chretien J., Masse R., Lafuma J. Lung cancerogenesis during in vivo cigarette smoking and radon daughter exposure in rats. Recent Results in Cancer Res. 1982. Vol. 82. PP. 11-20.

30. Dethlefsen L.A., Dewey W.C. (Eds.) Third International Symposium: Cancer Therapy by Hyperthermia, Drugs and Radiation. Bethesda: National Cancer Institute Monograph 61, 1982. 500 p.

31. Hahn G.W. Hyperthermia and Cancer. N.-Y., Plenum Press Publ., 1982. 285 p.

32. Haynes R.H. The interpretation of microbial inactivation and recovery phenomena. Radiat. Res. 1966. Suppl. 6. PP. 1-29.

33. Johnson H.A., Pavelec M. Thermal enhancement of thio-TEPA cytotoxicity. J. Natl. Cancer Inst. 1973. Vol. 50. PP. 903-908.

34. Kanno J., Onodera H., Furuta K., Maekawa A., Fasuga T., Hayashi Y. Tumor-promoting effects of both iodine deficience and iodine excess in the rat thyroid. Toxicol. Pathol. 1992. Vol. 20. PP. 226-235.

35. Kim J.K. Petin V.G. Theoretical conception of synergistic interactions. Korean J. Environ. Biol. 2002. Vol. 20. PP. 277-286.

36. Kim J.K., Petin V.G., Zhurakovskaya G.P. Exposure rate as a determinant of synergistic interaction of heat combined with ionizing or ultraviolet radiations in cell killing. J. Radiat. Res. 2001. Vol. 42. PP. 361-365.

37. Kumar A., Kiefer J., Schneider E., Crompton N.E.A. Inhibition of recovery from potentially lethal damage by chemicals in Chinese hamster V79 A cells. Radiat. Environ. Biophys. 1985. Vol. 24. PP. 89–98.

38. Kumar A., Kiefer J., Schneider E., Crompton N.E.A. Enhanced cell killing, inhibition of recovery from potentially lethal damage and increased mutation frequency by 3-aminobenzamide in Chinese hamster V79 cells exposed to X-rays. Int. J. Radiat. Biol. 1985. Vol. 47. PP. 103-112.

39. Leenhouts H.P., Chadwick K.H. An analysis of synergistic sensitisation. Br. J. Cancer. 1978. Vol. 37, Suppl. 3. PP. 198-201.

40. Leenhouts H.P., Sijsma M.J., Cebulska-Wasilewska A., Chadwick K.H. The combined effect of DBE and X-rays on the induction of somatic mutations in Tradescantia. Int. J. Radiat. Biol. 1986. Vol. 49. PP. 109-119.

41. Li G.C., Evans R.G., Hahn G.M. Modification and inhibition of repair of potentially lethal X-ray damage by hyperthermia. Radiat. Res. 1976. Vol. 67. PP. 491-501.

42. Murthy M.S.S., Deorukhakar V.V., Rao B.S. Hyperthermic inactivation of diploid yeast and interaction of damage caused by hyperthermia and ionizing radiation. Int. J. Radiat. Biol. 1979. Vol. 35. PP. 333-341.

43. Mills M.D., Meyn R.E. Effects of hyperthermia on repair of radiation-induced DNA strand breaks. Radiat. Res. 1981. Vol. 87. PP. 314-328.

44. Ohshima M., Ward J. Dietary iodine deficiency as a tumor promotor and carcinogen in male F344/NCr rats. Cancer Res. 1986. Vol. 46. PP. 877-883.

45. Pakhomova O.N., Tsyb T.S. Mutagenous effect and the mitotic crossing-over induction in yeasts under combined exposure to alpha-particles and gamma-rays. In: Molecular Mechanisms in Radiation Mutagenesis and Carcinogenesis. Eds. K.H. Chadwick, R. Cox, H.P. Leenhouts, J. Thacker. Brussels: European Commission, 1994. P. 203-206.

46. Petin V.G., Berdnikova I.P. Effect of elevated temperatures on the radiation sensitivity of yeast cells of different species. Radiat. Environm. Biophys. 1979. Vol. 16. PP. 49-61.

47. Petin V.G., Berdnikova I.P. Responses of yeast cells to heat applied alone or combined with gamma-rays. Int. J. Radiat. Biol. 1981. Vol. 39. PP. 281-290.

48. Petin V.G., Kim J.K. Universal rules of synergistic interaction and their significance in EMF application. WHO Meeting on EMF Biological Effects and Standards Harmonization in Asia and Oceania. Seoul, Korea, 2001. P. 116.

49. Petin V.G., Kim J.K., Rassokhina A.V., Zhurakovskaya G.P. Mitotic recombination and inactivation in Saccharomyces cerevisiae induced by (254 nm) radiation and hyperthermia depend on UV fluence rate. Mutation Research. 2001. Vol. 478. PP. 169-176.

50. Petin V.G., Kim J.K., Zhurakovskaya G.P., Dergacheva I.P. Some general regularities of synergistic interaction of hyperthermia with various physical and chemical inactivating agents. Int. J. Hyperthermia. 2002. Vol.18. PP. 40-49.

51. Petin V.G., Kim J.K., Zhurakovskaya G.P., Rassokhina A.V. Mathematical description of synergistic interaction of UV light and hyperthermia for yeast cells. J. Photochem. Photobiol. B: Biology. 2000. Vol. 55. PP. 74-79.

52. Petin V.G., Komarov V.P. Mathematical description of synergistic interaction of hyperthermia and ionizing radiation. Mathem. Biosci. 1997. Vol. 146. PP. 115-130.

53. Petin V.G., Zhurakovskaya G.P. The peculiarities of the interaction of radiation and hyperthermia in Saccharomyces cerevisiae irradiated with various dose rates. Yeast. 1995. Vol. 11. PP. 549-554.

54. Petin V.G., Zhurakovskaya G.P., Komarova L.N. Mathematical description of combined action of ultrasound and hyperthermia on yeast cells. Ultrasonics. 1999. Vol. 37. PP. 79-83.

55. Petin V.G., Zhurakovskaya G.P., Pantukhina, A.G., Rassokhina A.V. Low doses and problems of synergistic interaction of environmental factors. In: “Low Dose of Radiation: Are They Dangerous?” E.B. Burlakova (Editor). New York: Nova Science Publishers Inc, 2000. PP. 155-180.

56. Raaphorst G.P., Azzam E.I., Feeley M.M. Potentially lethal radiation damage repair and its inhibition by hyperthermia in normal hamster cells, mouse cells, and transformed mouse cells. Radiat. Res. 1988. Vol. 113. PP. 171-182.

57. Reynolds M.C., Brannen J.P. Thermal enhancement of radiosterilization. Radiation Preservation of Food. Vienna: International Atomic Energy Agency, 1973. P. 165-176.

58. Reynolds M.C., Garst D.M. Optimizing thermal and radiation effects for bacterial inactivation. Space Life Sci. 1970. Vol. 2. PP. 394-399.

59. Segaloff A., Pettigrew H.M. Effect of radiation dosage on the synergism between radiation and estrogen in the production of mammary cancer in the rat. Cancer Res. 1978. Vol. 38. PP. 3445-3452.

60. Shakhtarin V.V., Tsyb A.F., Stepanenko A.F., Lushnikov E.F., Snykov V.P., Orlov M.Yu., Trofimova S.F. Iodine deficiency and thyroid cancer morbidity following the accident at the Chernobyl power plant. Radiation and Thyroid Cancer. Ed. by G. Thomas, A. Karaoglou, E.D.  Williams. Singapure, New Jersey, London, Hong Kong: Word Scientific, 1999. PP. 277-282.

61. Stewart F.A., Denekamp J. Combined X-rays and heating: is there a therapeutic gain? In: Cancer Therapy by Hyperthermia and Radiation. Ed. by C. Streffer. Baltimore-Munich: Urban & Schwarzenberg, 1978. PP. 249-250.

62. Streffer С., Müller W.-U. Radiation risk from combined exposures to ionizing radiations and chemicals. Adv. Radiat. Biol. 1984. Vol. 11. PP. 173-210.

63. Streffer C., Vaupel P., Hahn G. Biological Basis of Oncologic Thermotherapy. Berlin: Springer Verlag, 1990. 418 p.

64. Tobias C.A. The repair-misrepair model in radiobiology: comparison to other models. Radiat. Res. 1985. Vol. 104, Suppl. 8, part 2. PP. 77-95.

65. Trujillo R., Dugan V.L. Synergistic inactivation of viruses by heat and ionizing radiations. Biophys. J. 1972. Vol. 12. PP. 92-113.

66. Urano M., Kahn J., Majima H., Gerweck L.E. The cytotoxic effect of cisdiamminedichloroplatinum (II) on culture Chinese hamster ovary cells at elevated temperatures: Arrhenius plot analysis. Int. J. Hyperthermia. 1990. Vol. 6. PP. 581-590.

67. Zaider, M., Rossi H.H. The synergistic effects of different radiations. Radiat. Res. 1980. Vol. 83. PP. 732-739.

68. Zyb A.F., Petin V.G., Rudakov I.A. Some regularities of cell radiosensitivity modification. Studia Biophysica. 1981. Vol. 86. PP. 43-44.

Full-text article (in Russian)